inflammatory responses and immune cell populations in skin explants - - PowerPoint PPT Presentation
inflammatory responses and immune cell populations in skin explants - - PowerPoint PPT Presentation
PUFA-derived bioactive lipids mediate inflammatory responses and immune cell populations in skin explants Alexandra Kendall Nordic LipidForum 6 th June 2015 SLS vs UVR SLS UVR Commonly encountered environmental stressors Exposure to high
SLS vs UVR Commonly encountered environmental stressors
- Exposure to high levels of SLS can causes irritant dermatitis
- - Dermatology/occupational health problem
- UVR is an alternative cause of skin erythema
- Do they affect the same lipid pathways?
UVR SLS
Ex vivo culture
Ex vivo treatment
Day 3 (morning): Culture medium replaced Day 2 (morning): Culture medium replaced Day 1 (evening): Delivery and processing of skin SDS-soaked disc applied Day 4 (morning): UVR applied Biopsies taken from centre of pieces of baseline and UV- and SLS-treated skin SDS-soaked disc removed Day 5 (morning):
Lipoxygenase products
12-lipoxygenase 15-lipoxygenase AA DHA DGLA EPA LA
12-HETE 11-HDHA 14-HDHA 12-HEPE 15-HETE 17-HDHA 15-HETrE 13-HODE
SLS 12-LOX products
12 HETE 12 HEPE 14 HDHA 11 HDHA 1 10 100 1000 10000 100000
Control 1% SDS 3% SDS 6% SDS
* * * * * * * *
pg/mg protein
15-LOX products
15 HETE 15 HETrE 13 HODE 17 HDHA 1 10 100 1000 10000
Control 1% SDS 3% SDS 6% SDS
* * * * * * * *
pg/mg protein n=4, mean ± SE * p<0.05
UVR 12-LOX products
12 HETE 12 HEPE 14 HDHA 11 HDHA 1 10 100 1000 10000
Control 4MED 6MED 10MED
pg/mg protein
15-LOX products
15 HETE 15 HETrE 13 HODE 17 HDHA 1 10 100 1000
Control 4MED 6MED 10MED
pg/mg protein n=4, mean ± SE
N-acyl ethanolamides
SLS
N-acyl ethanolamides
PEA ALEA LEA OEA STEA EPEA AEA DHEA DGLEA 1 10 100 1000 10000 100000 Control 1% SLS 3% SLS 6% SLS * * * * * pg/mg protein
n=4, mean ± SE * p<0.05
UVR
N-acyl ethanolamides
PEA ALEA LEA OEA STEA EPEA AEA DHEA DGLEA 1 10 100 1000 10000 Control 4MED 6MED 10MED pg/mg protein
n=4, mean ± SE
Immune cell population identification
SSC CD45 HLA-DR SSC CD1a CD14 SSC CD3 SSC TCRgd CD56 CD66b SSC CD127 Antigen presenting cells T cells NK cells Granulocytes Innate lymphoid cells
HLA-DR+ T cells Granulocytes NK cells ILCs HLA-DR+ T cells Granulocytes NK cells ILCs HLA-DR+ T cells Granulocytes NK cells ILCs HLA-DR+ T cells Granulocytes NK cells ILCs
Immune cell populations
- Inter-individual variation in response
- Consistent effect was reduction in innate lymphoid cell population
Despite similar clinical changes in vivo, SLS and UVR elicit different effects in skin explants
Conclusions
SLS UVR 12-LOX products Increase Non-significant increase 15-LOX products Increase No change N-acyl ethanolamides Increase No change Epidermal innate lymphoid cell population Decrease No change
Acknowledgements
University of Manchester Prof Anna Nicolaou Dr Amy Saunders Unilever SEAC Gary Sassano
This work was funded by Unilever as part of its
- ngoing program developing novel approaches